ArticleThe Journal of biological chemistry2023
FDX1 regulates cellular protein lipoylation through direct binding to LIAS.
Article in The Journal of biological chemistry, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 142 papers, 1 of them a synthesis that pooled it.
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Who cites it
142 citing papers in PubMed, 1 synthesis or guideline pooled it, 161 citations in OpenAlex.
- Cuproptosis as a therapeutic target in cancer: a Systematic Review and bibliometric analysis of the research landscape.Frontiers in oncology · 2025Pooled it
- The role of copper and cuproptosis in digestive system cancers: novel therapeutic strategies and mechanistic insights.Cancer biology & therapy · 2026Review
- Cuproptosis and the bioinorganic basis of copper-induced cell death.Journal of biological inorganic chemistry : JBIC : a publication of the Society of Biological Inorganic Chemistry · 2026Review
- Effects of cuproptosis and its application in inflammatory bowel disease (Review).International journal of molecular medicine · 2026Review
- Lactate metabolism regulation enhances cuproptosis to activate antitumor immunity: Synergistic therapy of hyaluronic acid nanomicelles delivering lactate oxidase/copper-doped carbon dots combined with α-PD-L1 inhibits distant tumors.Materials today. Bio · 2026Article
- Unveiling the pathogenesis and therapeutic strategies of Alzheimer's disease through cuproptosis.Biometals : an international journal on the role of metal ions in biology, biochemistry, and medicine · 2026Review
- GSH-responsive self-assembled nanoplatform synergistically enhances cuproptosis through metabolic reprogramming and oxidative stress amplification.Materials today. Bio · 2026Article
- Cuproptosis in Ischemic Stroke: Molecular Mechanisms and Therapeutic Potential.Molecules (Basel, Switzerland) · 2026Review
- Harnessing copper-iron crosstalk: A novel strategy to combat hepatocellular carcinoma.Medical oncology (Northwood, London, England) · 2026Review
- Copper, cuproptosis, and cancer: biology concepts of a novel cell death.Apoptosis : an international journal on programmed cell death · 2026Review
- Advances in ferroptosis and cuproptosis: implications for spinal cord injury.Molecular biology reports · 2026Review
- Review
- METTL14 Promotes Cuproptosis-Associated Changes in Rats With Myocardial Ischemia-Reperfusion Injury.Journal of cellular biochemistry · 2026Article
- DNA-damage-targeting copper nanoparticles induce cuproptosis for enhanced cancer radiotherapy.Materials today. Bio · 2026Article
- Engineering cuproptosis with nanomedicine: Design, combination therapy, and translation in cancer.Materials today. Bio · 2026Review
- Licochalcone a Disrupted Mitochondrial Function to Promote Cuproptosis in Glioblastoma Through Regulating RAS/MAPK Pathway.Applied biochemistry and biotechnology · 2026Article
- Redox-regulated cell death in gastric cancer: Molecular insights and therapeutic opportunities.Journal of physiology and biochemistry · 2026Review
- Targeting Copper in Cancer: Chelators to Counteract Cuproplasia and Ionophores to Promote Cuproptosis.Journal of medicinal chemistry · 2026Review
- UHRF1 inhibits cuproptosis in lung adenocarcinoma via promoting FDX1 promoter methylation.Respiratory research · 2026Article
- Copper homeostasis and cuproptosis rewire the tumor microenvironment: mechanisms, immune modulation, and therapeutic opportunities.Journal of hematology & oncology · 2026Review
82 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
Abstract
Ferredoxins are a family of iron-sulfur (Fe-S) cluster proteins that serve as essential electron donors in numerous cellular processes that are conserved through evolution. The promiscuous nature of ferredoxins as electron donors enables them to participate in many metabolic processes including steroid, heme, vitamin D, and Fe-S cluster biosynthesis in different organisms. However, the unique natural function(s) of each of the two human ferredoxins (FDX1 and FDX2) are still poorly characterized. We recently reported that FDX1 is both a crucial regulator of copper ionophore-induced cell death and serves as an upstream regulator of cellular protein lipoylation, a mitochondrial lipid-based post-translational modification naturally occurring on four mitochondrial enzymes that are crucial for TCA cycle function. Here we show that FDX1 directly regulates protein lipoylation by binding the lipoyl synthase (LIAS) enzyme promoting its functional binding to the lipoyl carrier protein GCSH and not through indirect regulation of cellular Fe-S cluster biosynthesis. Metabolite profiling revealed that the predominant cellular metabolic outcome of FDX1 loss of function is manifested through the regulation of the four lipoylation-dependent enzymes ultimately resulting in loss of cellular respiration and sensitivity to mild glucose starvation. Transcriptional profiling established that FDX1 loss-of-function results in the induction of both compensatory metabolism-related genes and the integrated stress response, consistent with our findings that FDX1 loss-of-function is conditionally lethal. Together, our findings establish that FDX1 directly engages with LIAS, promoting its role in cellular protein lipoylation, a process essential in maintaining cell viability under low glucose conditions.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.